The objectives of this application are to understand normal mammary development, the formation of mammary cancer, and the application of MoAbs in treatment of breast cancer using a model system in rats and studies of human breast cancer. (A) Rat model system. Studies on the development of MoAbs as immunological markers of individual cell types in the mammary gland will be extended by making MoAbs to pregnant and lactating mammary glands, which will complement those previously isolated. MoAbs selective for mammary epithelial cells will be used to establish a localization and therapy model using syngeneic transplantable mammary tumors of high or low metastatic potential. The evaluation will include effects of isotype, quantity, antibody fragments, route and regimen of administration, development of anti-mouse and anti-idiotype Abs. The oncogene status in chemically induced rat mammary tumors, both primaries and passaged tumors, will be determined. (B) Studies with human breast cancer. A panel on MoAbs raised against human breast cancer cell lines will be used to characterize antigens and their localization in cells and in the sera of patients. Xenografts of human breast tumors in nude mice will be used to study localization and anti-tumor effects of these MoAbs following the procedures established in the rat model. Cellular changes important for malignancy of human breast cancer will be studied from three different aspects. Tumorigenic and non-tumorigenic clones of human breast cancer cell lines will be compared for differences detectable by MoAbs or oncogene probes, Cells derived from patients with benign proliferative breast disease will be studied for changes in reactivity of MoAbs selective for breast carcinoma during serial transplantation to the parenchyma-free fat pads of nude mice. The acquisition of growth factor independence by breast cancer cells showing a strong density dependency of clony formation in methyl cellulose will be studied. We will purify the factor and determine its distribution and that of its receptors in normal and neoplastic breast epithelium.